Infection with hepatitis B virus is a major cause of liver disease worldwide and accounts for 5-10 per cent of chronic liver disease and cirrhosis in the United States. Safe and effective vaccines are now available for prevention of hepatitis B. However, therapies for the disease once it has occurred are unsatisfactory. Alpha interferon was the first antiviral agent shown to be effective in this disease and was licensed for this indication in the United States in 1993. The basis for licensure were, in part, studies conducted in the Liver Diseases Section of NIH. However, alpha interferon is effective in only one- third of patients with typical chronic hepatitis B and its role in atypical forms of this disease remain unclear. Current activities in the Liver Diseases Section are focused on developing better therapies to prevent long-term consequences. A pilot study of lamivudine for typical and atypical forms of chronic hepatitis B is being conducted. Patients with delta hepatitis have uniformly failed to respond to lamivudine. In contrast virtually all patients with chronic hepatitis B have had a serum biochemical, virological and histological response to lamivudine in a dose of 100 mg once daily. However, breakthrough with viral resistance has occurred in more than 50 percent of patients. Long-term safety and benefit of lamivudine are now being evaluated. Patients with viral resistance will be evaluated using new antivirals (adefovir) alone or in combination with lamivudine. Patients who have had a long term response to antiviral therapy will be evaluated for whether the virus is merely suppressed and is still present in low level or is eradication and no longer detectable even in liver. Immune responses to hepatitis antigens will be compared between long term responders and non responders to attempt to dissect out the immunology and virologic determinants of recovery from hepatitis B. - Antiviral/Interferon/Nucleoside Analog/Combination Therapy - Human Subjects